(a) Field of the Invention
This invention relates to a process for preparing 2-(aminoalkylthio)carbapenems. In particular, this invention relates to a process in which a bis(substituted phenyl) phosphorohalidate is used to form an enol phosphate intermediate that can be converted to 2-(aminoalkylthio)carbapenems by reaction with suitable thioalkylamines.
Certain of the 2-(aminoalkylthio)carbapenems prepared by the process of this invention are themselves esters of useful antibiotics, such as thienamycin. The 2-(aminoalkylthio)carbapenems prepared by the process of this invention may also be used as intermediates in the preparation of other useful carbapenem antibiotics, such as N-formamidoyl-thienamycin.
(b) Prior Art
Sletzinger et al., Tetrahedron Lett., 21, 4221-4224 (1980), have reported a procedure for converting a ketone carboxylate ester of Formula A ##STR1## to an enol phosphate intermediate of Formula B ##STR2## wherein R is ethyl or phenyl, and subsequently to a corresponding 8-epithienamycin derivative of Formula C. ##STR3## The process of the present invention uses various bis(chloro-substituted phenyl) phosphorochloridates to achieve surprisingly improved yields of n-formamidoylthienamycin relative to the corresponding unsubstituted diphenyl phosphorochloridate. See Table I, Example 5, below.